Chronic khat (Catha edulis) and alcohol marginally alter complete blood counts, clinical chemistry, and testosterone in male rats

Abstract

Introduction: Khat (Catha edulis) is a recreational psychoactive drug with psychostimulant properties. While the use of this drug is widespread in eastern Africa, including the Horn of Africa, surveys and anecdotal data show that its use has become cosmopolitan, with users now living in Europe and North America as well. Recent data in Uganda suggest an increasing pattern of simultaneous khat and ethanol use particularly among young adults. However, the effects of this pattern of use remain largely unknown, even though long-term use of either drug alone is known to be harmful. The aim of this study was to examine the toxic effects of simultaneous chronic administration of khat and ethanol on hematological parameters, clinical chemistry, and testosterone in a rat model.

Methods: Adult male Sprague-Dawley rats were randomly assigned to one of six dose groups: 2 g/kg khat; 4 g/kg khat; 4 g/kg ethanol; combined khat and ethanol (4 g/kg each); control; and an untreated group. Treatments were given by gavage twice daily for 28 days, followed by determination of hematological parameters, blood clinical chemistry, and testosterone.

Results: Ethanol alone significantly reduced platelet counts compared to control-, untreated and low-dose khat-treated rats; conversely low-dose khat significantly increased both the hemoglobin and hematocrit values, while ethanol alone also significantly increased the hemoglobin value compared to controls. Simultaneous khat and ethanol administration per se did not produce more toxic consequences in chronic use than either drug alone.

Conclusion: Chronic short-term khat use and ethanol dependence individually produce note-worthy effects on the blood, but not on clinical chemistry or testosterone. Chronic short-term combined khat and ethanol use does not produce more toxic effects compared to use of either drug alone. This provides an opportunity for appropriate clinical interventions to avert the chronic long-term effects that result from use of these drugs of abuse.

Keywords: chemistry; chronic; ethanol; hematology; khat; testosterone.

Figure 1

Body weights of experimental animals. Notes: Body weights of experimental animals (grams), shown as mean ± standard error of the mean. All animals showed a modest weight gain. There was no statistical difference in body weight between the treatment groups at the beginning of the experiment and at 28 days of treatment. However, on day 24, there was a trend towards a significant difference in body weights (P = 0.059) which persisted to day 28 (P = 0.062). Abbreviation: EtOH, ethanol.

Figure 2

Blood cell counts of male rats after 28 days of treatment. Notes: (A) White blood cell counts of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment, shown as mean ± standard error of the mean. There was no statistical difference between the treatment groups. (B) Red blood cell counts of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. There was no statistical difference between the treatment groups. (C) Platelet counts of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. Ethanol treatment significantly reduced the platelet count compared to 2 g/kg khat treatment and control and untreated rats; ^aP < 0.05, comparing 20% ethanol and untreated animals; ^bP < 0.05, comparing 20% ethanol and control animals; *P < 0.05, comparing 20% ethanol and 2 g/kg khat. (D) Red blood cell distribution width of different treatments at 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. There was no statistical difference between the treatment groups. Abbreviations: kh, khat; EtOH, ethanol.

Figure 3

Mean corpuscular values of male rats after 28 days of treatment. Notes: (A) Mean corpuscular volume of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment, shown as mean ± standard error of the mean. There was no statistical difference between the treatment groups. (B) Mean corpuscular hemoglobin of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. There was no statistical difference between the treatment groups. (C) Mean corpuscular hemoglobin concentration of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. There was no statistical difference between the treatment groups. (D) Mean platelet volume of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. There was no statistical difference between the treatment groups. Abbreviations: kh, khat; EtOH, ethanol.

Figure 4

Hemoglobin and hematocrit levels of male rats after 28 days of treatment. Notes: (A) Hemoglobin levels of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment, shown as mean ± standard error of the mean. Both 2 g/kg khat and 20% ethanol significantly increased Hb compared to control treatment. *P < 0.05 comparing 2 g/kg khat to control; **P < 0.05 comparing 20% ethanol to control. (B) Hematocrit values of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. 2 g/kg khat significantly increased hematocrit compared to control treatment. ***P < 0.05 comparing 2 g/kg khat and control. Abbreviations: kh, khat; EtOH, ethanol.

Figure 5

Serum enzyme levels of male rats after 28 days of treatment. Notes: (A) Serum amylase of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment, shown as mean ± standard error of the mean. There was no statistical difference between the treatment groups. (B) Serum alkaline phosphatase of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. There was no statistical difference between the treatment groups. (C) Serum aspartate aminotransferase of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. There was no statistical difference between the treatment groups although there was a trend towards a significant ethanol effect (P = 0.061). (D) Serum alanine aminotransferase of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. There was no statistical difference between the treatment groups. DGKC is a method for the determination of alkaline phosphatase (ALP) from the German Society of Clinical Chemistry [Deutsche Gesellschaft fur Klinische Chemie]. Abbreviations: ALP, alkaline phosphatase; GOT, glutamic oxaloacetic transaminase; AST, aspartate aminotransferase; GPT, glutamic pyruvate transaminase; ALT, alanine aminotransferase; kh, khat; EtOH, ethanol; DGKC, [Deutsche Gesellschaft fur Klinische Chemie]; German Society of Clinical Chemistry method.

Figure 6

Serum creatinine, albumin and lipoprotein levels of male rats after 28 days of treatment. Notes: (A) Serum creatinine of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment, shown as mean ± standard error of the mean. There was no statistical difference between the treatment groups. (B) Serum albumin of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. There was no statistical difference between the treatment groups. (C) Serum high density lipoprotein of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. There was no statistical difference between the treatment groups. (D) Serum low density lipoprotein of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment. There was no statistical difference between the treatment groups. Abbreviations: kh, khat; EtOH, ethanol; LDL, low density lipoproteins; HDL, high density lipoproteins.

Figure 7

Total serum testosterone in male rats after 28 days of treatment. Notes: Serum testosterone of male rats after 28 days of 2 g/kg khat, 4 g/kg khat, 20% ethanol, 20% ethanol plus khat, control, and no treatment, shown as mean ± standard error of the mean. There was no statistical difference between the treatment groups. Abbreviations: kh, khat; EtOH, ethanol.